Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

The bear in Eurasian plant names: Motivations and models

Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g. whether they form common heritage, have an independent origin, are borrowings, or calques. The current study was conducted on the material in Slavonic, Baltic, Germanic, Romance, Finno-Ugrian, Turkic and Albanian languages. The bear was chosen as being a large, dangerous animal, important in traditional culture, whose name is widely reflected in folk plant names. The phytonyms for comparison were mostly obtained from dictionaries and other publications, and supplemented with data from databases, the co-authors' field data, and archival sources (dialect and folklore materials). More than 1200 phytonym use records (combinations of a local name and a meaning) for 364 plant and fungal taxa were recorded to help find out the reasoning behind bear-nomination in various languages, as well as differences and similarities between the patterns among them. Among the most common taxa with bear-related phytonyms were Arctostaphylos uva-ursi (L.) Spreng., Heracleum sphondylium L., Acanthus mollis L., and Allium ursinum L., with Latin loan translation contributing a high proportion of the phytonyms. Some plants have many and various bear-related phytonyms, while others have only one or two bear names. Features like form and/or surface generated the richest pool of names, while such features as colour seemed to provoke rather few associations with bears. The unevenness of bear phytonyms in the chosen languages was not related to the size of the language nor the present occurence of the Brown Bear in the region. However, this may, at least to certain extent, be related to the amount of the historical ethnolinguistic research done on the selected languages

Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin &ndash; a model-based study

Thomas Edrich,1,2 Gyorgy Frendl,2 Gregory Michaud,3 Ioannis Ch Paschalidis4 1Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria, 2Department of Anesthesiology, Perioperative and Pain Medicine, 3Department of Medicine, Division of Cardiology, Brigham and Women&#39;s Hospital, Harvard Medical School, 4Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, Boston, MA, USA Purpose: Dabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation. Patients and methods: In a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups. Results: Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P&lt;0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups. Conclusion: Patients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin. Keywords: atrial fibrillation, electrophysiology, NONMEM, PKPD mode

Postoperative Pulmonary Complications, Early Mortality, and Hospital Stay Following Noncardiothoracic Surgery

IMPORTANCE: Postoperative pulmonary complications (PPCs), a leading cause of poor surgical outcomes, are heterogeneous in their pathophysiology, severity, and reporting accuracy. OBJECTIVE: To prospectively study clinical and radiological PPCs and respiratory insufficiency therapies in a high-risk surgical population. DESIGN, SETTING, AND PARTICIPANTS: We performed a multicenter prospective observational study in 7 US academic institutions. American Society of Anesthesiologists physical status 3 patients who presented for noncardiothoracic surgery requiring 2 hours or more of general anesthesia with mechanical ventilation from May to November 2014 were included in the study. We hypothesized that PPCs, even mild, would be associated with early postoperative mortality and use of hospital resources. We analyzed their association with modifiable perioperative variables. EXPOSURE: Noncardiothoracic surgery. MAIN OUTCOMES AND MEASURES: Predefined PPCs occurring within the first 7 postoperative days were prospectively identified. We used bivariable and logistic regression analyses to study the association of PPCs with ventilatory and other perioperative variables. RESULTS: This study included 1202 patients who underwent predominantly abdominal, orthopedic, and neurological procedures. The mean (SD) age of patients was 62.1 (13.8) years, and 636 (52.9%) were men. At least 1 PPC occurred in 401 patients (33.4%), mainly the need for prolonged oxygen therapy by nasal cannula (n = 235; 19.6%) and atelectasis (n = 206; 17.1%). Patients with 1 or more PPCs, even mild, had significantly increased early postoperative mortality, intensive care unit (ICU) admission, and ICU/hospital length of stay. Significant PPC risk factors included nonmodifiable (emergency [yes vs no]: odds ratio [OR], 4.47, 95% CI, 1.59–12.56; surgical site [abdominal/pelvic vs nonabdominal/pelvic]: OR, 2.54, 95% CI, 1.67–3.89; and age [in years]: OR, 1.03, 95% CI, 1.02–1.05) and potentially modifiable (colloid administration [yes vs no]: OR, 1.75, 95% CI, 1.03–2.97; preoperative oxygenation: OR, 0.86, 95% CI, 0.80–0.93; blood loss [in milliliters]: OR, 1.17, 95% CI, 1.05–1.30; anesthesia duration [in minutes]: OR, 1.14, 95% CI, 1.05–1.24; and tidal volume [in milliliters per kilogram of predicted body weight]: OR, 1.12, 95% CI, 1.01–1.24) factors. CONCLUSIONS AND RELEVANCE: Postoperative pulmonary complications are common in patients with American Society of Anesthesiologists physical status 3, despite current protective ventilation practices. Even mild PPCs are associated with increased early postoperative mortality, ICU admission, and length of stay (ICU and hospital). Mild frequent PPCs (eg, atelectasis and prolonged oxygen therapy need) deserve increased attention and intervention for improving perioperative outcomes